Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder that can cause substantial impairment in family/social relationships and the ability to succeed in school and occupation; yet, fundamental aspects of the neurobiology of ADHD remain poorly understood. Anomalous motor development is a consistent, but infrequently studied characteristic observed with ADHD that can provide insight into the neurologic basis of the disorder. Children with ADHD fail to meet age-norms on timed repetitive and sequential movements and manifest a greater amount of motor overflow than age-matched controls. These findings, which can accurately distinguish ADHD children from normal controls and children with other neuropsychiatric disorders, suggest that ADHD is associated with abnormalities of motor cortex inhibitory systems. Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) can localize and quantify inhibition within the motor cortex and thus are particularly suited to study motor inhibition in ADHD. We hypothesize that the neuromotor anomalies present in children with ADHD are associated with deficient intracortical and interhemispheric inhibition of the motor cortex. This hypothesis is consistent with studies suggesting that the central deficit of ADHD is a failure to inhibit or delay a behavioral response. Our preliminary studies using both fMRI and TMS suggest that abnormalities of motor cortex inhibition are present in children with ADHD. The overall goal of this project is to investigate the neurologic basis of motor anomalies associated with ADHD. We propose three specific aims. In the first aim we will measure overflow movements using electromyography (EMG) and accelerometry, which will allow us to detect meaningful correlations between overflow measurements and neurophysiologic and imaging data. The second aim will focus on examining motor cortex inhibition using TMS. The third aim will assess patterns of fMRI activation during simple finger movements, including activation patterns associated with overflow movements. We will then examine the relationship between abnormalities of cortical inhibition and measures of hyperactivity and inattention. The data from these studies will yield critical insights into the neurobiological basis of ADHD and will also set the stage for future development of more effective therapies for this population. [unreadable] [unreadable] [unreadable] [unreadable]